Journal
HUMAN MOLECULAR GENETICS
Volume 21, Issue 19, Pages 4162-4170Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/dds232
Keywords
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Funding
- National Institutes of Health [GM083337]
- European Research Council
- EMBO Young Investigator Programme
- Hutchinson Whampoa
- Cancer Research, UK
- University of Cambridge
- Cancer Research UK [15603] Funding Source: researchfish
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In multicellular organisms, developmental changes to replication timing occur in 400800 kb domains across half the genome. While examples of epigenetic control of replication timing have been described, a role for DNA sequence in mammalian replication-timing regulation has not been substantiated. To assess the role of DNA sequences in directing developmental changes to replication timing, we profiled replication timing in mice carrying a genetically rearranged Human Chromosome 21 (Hsa21). In two distinct mouse cell types, Hsa21 sequences maintained human-specific replication timing, except at points of Hsa21 rearrangement. Changes in replication timing at rearrangements extended up to 900 kb and consistently reconciled with the wild-type replication pattern at developmental boundaries of replication-timing domains. Our results are consistent with DNA sequence-driven regulation of Hsa21 replication timing during development and provide evidence that mammalian chromosomes consist of multiple independent units of replication-timing regulation.
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